PulmoVascular Remodelling

Pulmonary Vascular Remodeling in COPD

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lungs that has been a major public health problem, and has been the third leading cause of death worldwide. A large proportion of COPD deaths (~75%) are linked to tobacco smoking, which is now the primary risk factor in the development of the disease. It was reported that exposure to tobacco smoke (TS) causes significant increase in the thickness of the smooth layers of airway and also induces generation of reactive oxygen species in COPD rodent models. Indeed, airway and pulmonary vascular remodeling are one of the key characteristics found in the pathogenesis of COPD. This phenomenon leads to airflow obstruction and pulmonary hypertension linked to this smooth muscle cell proliferation and an accumulation of extracellular matrix such as collagen.

Reactive oxygen species, such as hydrogen peroxide, play an important role in the pathological growth of COPD as they also participate in this process of vascular remodeling. Their formation was found to be increased in the bronchi and pulmonary arteries of mice exposed to TS. The specific mechanism involved is yet to be determined. However, in recent studies conducted by Zhu et al, calpain (cysteine endopeptidase) proved to be activated in a major manner in the smooth muscle of airway and vascular pulmonary arterioles of lungs in COPD rodent models induced by TS.

In addition, Zhu’s team investigated the effects of a smooth muscle-specific knock out of calpain and an inhibitor of calpain. Using the flexiVent and particularly its SnapShot manoeuvre, readings of airway resistance were done on the TS-induced COPD mice models. In both cases, results showed an attenuation of the previous increase in airway resistance seen in the TS-induced COPD mice models. This favorably indicates that airway and pulmonary vascular remodeling in COPD is mediated in a certain way by a ROS-dependent calpain activation initiated by tobacco smoke inhalation. The inhibition of calpain could then be an interesting new research approach to ameliorate airway thickening and obstruction observed in COPD and to better understand its underlying functioning.

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